Cigarette smoking, alcohol intake, and thyroid cancer risk: a pooled analysis of five prospective studies in the United States

Objective

We examined the associations between cigarette smoking, alcohol intake, and thyroid cancer risk in a pooled analysis of five prospective studies.

Methods

Data from five prospective U.S. studies were standardized and then combined into one aggregate dataset (384,433 men and 361,664 women). Pooled hazard ratios (HR) and 95?% confidence intervals (CI) for thyroid cancer were estimated from mutually adjusted models of cigarette smoking and alcohol intake, which were additionally adjusted for age, sex, education, race, marital status, body mass index, and cohort.

Results

Over follow-up, 1,003 incident thyroid cancer cases (335 men and 668 women) were identified. Compared to never smokers, current smoking was associated with reduced risk of thyroid cancer (HR?=?0.68, 95?% CI 0.55–0.85); this association was slightly stronger among non-drinkers (HR?=?0.46, 95?% CI 0.29–0.74). No reduction in risk was observed for former, compared to never, smokers. Greater smoking intensity, duration, and pack-years were associated with further reductions in risk among former and current smokers. Alcohol intake was also inversely associated with thyroid cancer risk (≥7 drinks/week versus 0, HR?=?0.72, 95?% CI 0.58–0.90, p trend?=?0.002). Inverse associations with smoking and alcohol were more pronounced for papillary versus follicular tumors.

Conclusion

The results of this pooled analysis suggest that both cigarette smoking and alcohol consumption are associated with reduced risks of papillary thyroid cancer and, possibly, follicular thyroid cancer.     

Risk factors for colon cancer in 150,912 postmenopausal women

Background

Prospective data from the Women’s Health Initiative were analyzed to evaluate more than 800 possible risk factors for an association with colon cancer in postmenopausal women.

Methods

Data included 150,912 postmenopausal women between the ages of 50 and 79. The Cox proportional hazard regression analysis was used to identify risk factors independently associated with the development of colon cancer during a median follow-up time of 8?years.

Results

A total of 1,210 women developed colon cancer and 282 developed rectal cancer. Eleven risk factors were independently associated with an increased risk of colon cancer at the p?2 values, they were age, waist girth (especially for subjects without diabetes), use of hormone therapy at baseline (protective), years smoked, arthritis (protective presumably because of medications used for treatment), relatives with colorectal cancer, lower hematocrit levels, fatigue, diabetes, less use of sleep medication, and cholecystectomy. Of the 11 factors, three were significantly associated with an increased risk of rectal cancer: age, waist, and not taking hormone therapy.

Conclusions

The results provide additional support for the importance of waist girth, hormone therapy, smoking, NSAID use, diabetes, and cholecystectomy as risk factors for colon cancer. Some factors previously identified as influencing risk (exercise and black race) did not have a strong independent association with colon cancer in this analysis.     

Body size across the life course and risk of premenopausal and postmenopausal breast cancer in Black women,the Carolina Breast Cancer Study, 1993–2001

Background

It is believed that greater adiposity is associated with reduced risk of breast cancer in premenopausal but increased risk in postmenopausal women. However, few studies have evaluated these relationships among Black women or examined anthropometric measures other than near-diagnosis body mass index (BMI).

Purpose

This study investigated associations between measures of body size across the life course and breast cancer risk among Black and White women living in the US South.

Methods

We used data from the Carolina Breast Cancer Study, a population-based case–control study of invasive breast cancer in North Carolina women aged 20–74 years. We assessed nine body size variables, including age 10 relative weight; age 18 BMI; adult weight gain; “reference” BMI 1 year before interview; and post-diagnosis measured BMI and abdominal obesity measures.

Results

Among premenopausal Whites, heavier childhood relative weight was associated with decreased cancer risk [odds ratio (OR) 0.48 95 % confidence interval 0.33–0.70]. Among premenopausal Blacks, greater adult waist circumference and waist-to-hip ratio (WHR) were associated with increased risk [waist OR 1.40 (1.00–1.97) and high tertile WHR OR 2.03 (1.29–3.19)], with associations for WHR in a similar direction in Whites. Among postmenopausal women, recalled body size was not associated with risk, except for increased risk associated with adult weight gain among White non-hormone therapy users. ER/PR status and hormone therapy use also modified other associations.

Discussion

In this population, greater adult BMI was not associated with increased breast cancer risk, but some measures of early-life body size and abdominal obesity were associated with risk.     

Association between lifestyle,menstrual/reproductive history,and histological factors and risk of breast cancer in women biopsied for benign breast disease

Purpose

Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD.

Methods

We conducted a case–control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case–control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression.

Results

Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39–0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68–7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05–15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer.

Conclusion

This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.

     

Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics

Background

Though mammographic density (MD) has been proposed as an intermediate marker of breast cancer risk, few studies have examined whether the associations between breast cancer risk factors and risk are mediated by MD, particularly by tumor characteristics.

Methods

Our study population included 3392 cases (1105 premenopausal) and 8882 (3192 premenopausal) controls from four case–control studies. For established risk factors, we estimated the percent of the total risk factor association with breast cancer that was mediated by percent MD (secondarily, by dense area and non-dense area) for invasive breast cancer as well as for subtypes defined by the estrogen receptor (ER+/ER?), progesterone receptor (PR+/PR?), and HER2 (HER2+/HER2?). Analyses were conducted separately in pre- and postmenopausal women.

Results

Positive associations between prior breast biopsy and risk of invasive breast cancer as well as all subtypes were partially mediated by percent MD in pre- and postmenopausal women (percent mediated?=?11–27%, p?≤?0.02). In postmenopausal women, nulliparity and hormone therapy use were positively associated with invasive, ER+?, PR+?, and HER2? breast cancer; percent MD partially mediated these associations (percent mediated?≥?31%, p?≤?0.02). Further, among postmenopausal women, percent MD partially mediated the positive association between later age at first birth and invasive as well as ER+?breast cancer (percent mediated?=?16%, p?≤?0.05).

Conclusion

Percent MD partially mediated the associations between breast biopsy, nulliparity, age at first birth, and hormone therapy with risk of breast cancer, particularly among postmenopausal women, suggesting that these risk factors at least partially influence breast cancer risk through changes in breast tissue composition.

     

Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women

Background

It is known that use of hormone replacement therapy (HRT) by postmenopausal women increases the risk of breast cancer.

Method

In this study, oestrogen receptor (ER)-α expression is examined using standard immunoperoxidase technique.

Results

Normal breast samples of 11 Australian postmenopausal women have been included in the ER-α study; the result showed a strong correlation (r ² = 0.80) between ER-α expression in normal breast epithelial cells and body mass index (BMI) in normal women who currently use HRT.

Conclusion

This finding confirms that the possibility of increased risk of breast cancer associated with increased ER-α expression in normal breast epithelial cells, in turn associated with high BMI and the use of HRT.     

A prospective study of reproductive factors and exogenous hormone use in relation to ovarian cancer risk among Black women

Purpose

Extensive data in White women have linked oral contraceptive use, tubal ligation, and parity to reduced risk of ovarian cancer; results on postmenopausal female hormone use are mixed. Few studies, all of which are case–control studies, have been undertaken among Black women. The aim of the present study was to prospectively assess associations of reproductive factors and exogenous hormones with ovarian cancer among Black women.

Methods

During follow-up from 1995 to 2013 in the Black Women’s Health Study, a prospective cohort study, 115 incident cases of ovarian cancer were identified. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the relation of the factors of interest to risk of ovarian cancer, with control for covariates.

Result

Oral contraceptive use was inversely associated with ovarian cancer risk: The HR for ≥10 years of use relative to <1 year was 0.50 (95% CI 0.30–0.98). For postmenopausal female hormone use, the HRs for ever use of estrogen with progestin and of estrogen alone were 1.37 (0.73–2.55) and 1.66 (0.90–3.07), respectively. The HRs for parity and tubal ligation were below 1.0, but were not statistically significant.

Conclusion

Overall, the findings indicate that the relation of reproductive factors and exogenous hormone use to risk of ovarian cancer is similar among Black and White women. The results on estrogen-only supplements and estrogen with progestin supplements add to evidence from Whites, indicating that use of hormone supplements may be associated with increased risk of ovarian cancer.

     

Association of reproductive history with breast tissue characteristics and receptor status in the normal breast

Introduction

Reproductive history has been associated with breast cancer risk, but more knowledge of the underlying biological mechanisms is needed. Because of limited data on normal breast tissue from healthy women, we examined associations of reproductive history and established breast cancer risk factors with breast tissue composition and markers of hormone receptors and proliferation in a nested study within the Karolinska Mammography project for risk prediction for breast cancer (Karma).

Materials and methods

Tissues from 153 women were obtained by ultrasound-guided core needle biopsy as part of the Karma project. Immunohistochemical staining was used to assessed histological composition of epithelial, stromal and adipose tissue, epithelial and stromal oestrogen receptor (ER) and progesterone receptor (PR) status, and Ki-67 proliferation status. An individualised reproductive score including parity, number of pregnancies without birth, number of births, age at first birth, and duration of breastfeeding, was calculated based on self-reported reproductive history at the time of the Karma study entry. All analyses were adjusted for age and BMI.

Results

Cumulated reproductive score was associated with increased total epithelial content and greater expression of epithelial ER. Parity was associated with greater epithelial area, increased epithelial–stromal ratio, greater epithelial ER expression and a lower extent of stromal proliferation. Increasing numbers of pregnancies and births were associated with a greater epithelial area in the entire study set, which remained significant among postmenopausal women. Increasing numbers of pregnancies and births were also associated with a greater expression of epithelial ER among postmenopausal women. Longer duration of breastfeeding was associated with greater epithelial area and greater expression of epithelial PR both in the entire study set and among postmenopausal women. Breastfeeding was also positively associated with greater epithelial ER expression among postmenopausal women. Prior use of oral contraceptives was associated with lower epithelial–stromal ratio amongst all participants and among pre- and postmenopausal women separately.

Conclusion

Reproductive risk factors significantly influence the epithelial tissue compartment and expression of hormone receptors in later life. These changes remain after menopause. This study provides deeper insights of the biological mechanisms by which reproductive history influences epithelial area and expression of hormone receptors, and as a consequence the risk of breast cancer.

     

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study

Introduction

Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T→C polymorphism.

Methods

Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses.

Results

We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A ₂/A ₂ genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A ₁/A ₁ (wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions.

Conclusion

We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene-environment interactions.     

Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy

Objective

Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT.

Methods

A nested case–control study was conducted within the prospective Danish population-based ‘Diet, Cancer, and Health’ cohort. During follow-up, 348 eligible cases were identified among 20,861 postmenopausal women and matched to 348 controls. Baseline serum samples were analyzed for estradiol, bioavailable estradiol, estrone, estrone sulfate, and SHBG. Conditional logistic regression yielded incidence rate ratios and 95?% confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders.

Results

Modest direct associations were identified between estrogen levels and breast cancer incidence among both never and baseline HRT users. Estrone and estrone sulfate were more consistently associated among both groups than estradiol. No association was found with SHBG.

Conclusion

Despite different hormonal profiles, higher serum estrogen levels were associated with a higher risk of breast cancer among both never and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.     

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women

Purpose

Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes.

Methods

We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2?) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype.

Results

We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype.

Conclusions

The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.     

Reproductive factors and risk of contralateral breast cancer by BRCA1 and BRCA2 mutation status: results from the WECARE study

Objective

Reproductive factors, such as early age at menarche, late age at menopause, and nulliparity are known risk factors for breast cancer. Previously, we reported these factors to be associated with risk of developing contralateral breast cancer (CBC). In this study, we evaluated the association between these factors and CBC risk among BRCA1 and BRCA2 (BRCA1/2) mutation carriers and non-carriers.

Methods

The WECARE Study is a population-based multi-center case–control study of 705 women with CBC (cases) and 1,397 women with unilateral breast cancer (controls). All participants were screened for BRCA1/2 mutations and 181 carriers were identified. Conditional logistic regression models were used to evaluate associations between reproductive factors and CBC for mutation carriers and non-carriers.

Results

None of the associations between reproductive factors and CBC risk differed between mutation carriers and non-carriers. The increase in risk with younger age at menarche and decrease in risk in women with more than two full-term pregnancies seen in non-carriers were not significantly different in carriers (adjusted RRs = 1.31, 95% CI 0.65–2.65 and 0.53, 95% CI 0.19–1.51, respectively). No significant associations between the other reproductive factors and CBC risk were observed in mutation carriers or non-carriers.

Conclusion

For two reproductive factors previously shown to be associated with CBC risk, we observed similar associations for BRCA1/2 carriers. This suggests that reproductive variables that affect CBC risk may have similar effects in mutation carriers and non-carriers.     

Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study

Background

Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women.

Methods

We examined relationships among 190,872 postmenopausal women, ages 50–71 years recruited during 1995–1996 for the NIH-AARP Diet and Health Study, in whom 7,384 incident invasive breast carcinomas were identified through 2006. Multivariable Cox regression hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated for breast cancer risk factors by age (50–59, 60–69, ≥70 years).

Results

The only factor showing significant statistical heterogeneity by age (p _het = 0.001) was menopausal hormone therapy duration, but trends were apparent across all ages and the strongest association prevailed among women 60–69 years. Although other risk factors did not show statistically significant heterogeneity by age, we did observe attenuated relations for parity and late age at first birth among older women [e.g., HR for age at first birth ≥30 vs. 20–24 = 1.62 (95 % CI 1.23–2.14) for women 50–59 years vs. 1.12 (0.96–1.31) for ≥70 years]. In contrast, risk estimates associated with alcohol consumption and BMI tended to be slightly stronger among the oldest subjects [e.g., HR for BMI ≥35 vs. 18.5–24.9 = 1.24 (95 % CI 0.97–1.58) for 50–59 years vs. 1.46 (1.26–1.70) for ≥70 years]. These differences were somewhat more pronounced for estrogen receptor positive and ductal cancers, tumors predominating among older women. Breast cancer family history, physical activity, and previous breast biopsies did not show divergent associations by age.

Conclusion

Although breast cancer risk factor differences among older women were not large, they may merit further consideration with respect to individualized risk prediction.     

Body weight in early adulthood,adult weight gain,and risk of endometrial cancer in women not using postmenopausal hormones

Purpose

High body mass index (BMI) measured in middle age or later is an established risk factor for endometrial cancer. However, whether BMI measured in early adulthood and adult weight change are associated with endometrial cancer risk is less clear, particularly among nonusers of postmenopausal hormones (PMH).

Methods

These associations were investigated among women in the Cancer Prevention Study II Nutrition Cohort. Women taking PMH (n = 11,624, 12 % of all women) were excluded, and the analysis was limited to 33,057 postmenopausal women who did not take PMH. Between enrollment in 1992/1993 and 30 June 2009, 447 women were diagnosed with endometrial cancer. Cox proportional hazards regression was used to calculate hazard rate ratios (RR) and corresponding 95 % confidence intervals (CI) for the association of BMI at age 18, calculated from recalled weight, and weight change between age 18 and 1992, with endometrial cancer incidence.

Results

BMI at age 18 was associated with higher risk of endometrial cancer in multivariable models adjusted for other risk factors (RR 1.29, 95 % CI 1.12–1.49 per 5 BMI units). Similarly, adult weight change was associated with higher risk of endometrial cancer (RR 1.81, 95 % CI 1.66–1.98 per 5 BMI unit change) in multivariable models adjusted for other risk factors.

Conclusions

High BMI at age 18 and greater adult weight gain were strongly associated with risk of endometrial cancer. These results underscore the importance of both avoiding overweight/obesity in young adulthood and preventing weight gain thereafter to minimize risk of this cancer.     

Urinary bisphenol A-glucuronide and postmenopausal breast cancer in Poland

Purpose

Concerns regarding a possible link between bisphenol A (BPA) and breast cancer have been mounting, but studies in human populations are lacking. We evaluated the association between the major urinary BPA metabolite [BPA-glucuronide (BPA-G)] and postmenopausal breast cancer risk in a large population-based case–control study conducted in two cities in Poland (2000–2003); we further explored the association of BPA-G levels with known postmenopausal breast cancer risk factors in our control population.

Methods

We analyzed creatinine-adjusted urinary BPA-G levels among 575 postmenopausal cases matched on age and study site to 575 controls without breast cancer using a recently developed assay. Odds ratios and 95 % confidence intervals were used to estimate the association between urinary BPA-G level and breast cancer using conditional logistic regression. Among controls, geometric mean BPA-G levels were compared across categories of breast cancer risk factors using linear regression models.

Results

There was no indication that increased BPA-G was associated with postmenopausal breast cancer (p-trend = 0.59). Among controls, mean BPA-G was higher among women reporting extended use of menopausal hormones, a prior screening mammogram, and residence in Warsaw. Other comparisons across strata of postmenopausal breast cancer risk factors were not related to differences in BPA-G.

Conclusions

Urinary BPA-G, measured at the time of diagnosis, is not linked to postmenopausal breast cancer.     

The Association of Reproductive and Lifestyle Factors with a Score of Multiple Endogenous Hormones

Introduction

We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously.

Methods

This cross-sectional analysis included 738 postmenopausal Nurses’ Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone’s age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models.

Results

The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation?=?2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p?p?=?0.0004). Family history of breast cancer, age at menarche, and physical activity were not associated with the score.

Conclusions

Reproductive breast cancer risk factors were not associated with elevated levels of multiple endogenous hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones.     

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.

Methods:

We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.

Results:

Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.

Conclusion:

This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.     

Body size in early life and breast cancer risk in African American and European American women

Purpose

There is growing evidence that body size in early life influences lifetime breast cancer risk, but little is known for African American (AA) women.

Methods

We evaluated body size during childhood and young adulthood and breast cancer risk among 1,751 cases [979 AA and 772 European American (EA)] and 1,673 controls (958 AA and 715 EA) in the Women’s Circle of Health Study. Odds ratio (OR) and 95 % confidence intervals (CI) were computed using logistic regression models while adjusting for potential covariates.

Results

Among AA women, being shorter at 7–8 years compared to peers was associated with increased postmenopausal breast cancer risk (OR 1.68, 95 % CI 1.02–2.74), and being heavier at menarche with decreased postmenopausal breast cancer risk, although of borderline significance (OR 0.45, 95 % CI 0.20–1.02). For EA women, being shorter from childhood through adolescence, particularly at menarche, was associated with reduced premenopausal breast cancer risk (OR 0.55, 95 % CI 0.31–0.98). After excluding hormone replacement therapy users, an inverse association with postmenopausal breast cancer was found among EA women reporting to be heavier than their peers at menarche (OR 0.18, 95 % CI 0.04–0.79). The inverse relationship between BMI at age 20 and breast cancer risk was stronger and only statistically significant in EA women. No clear association with weight gain since age 20 was found.

Conclusions

Findings suggest that the impact of childhood height on breast cancer risk may differ for EA and AA women and confirm the inverse association previously reported in EA populations with adolescent body fatness, in AA women.     

Prolactin serum levels and breast cancer: relationships with risk factors and tumour characteristics among pre- and postmenopausal women in a population-based case–control study from Poland

Background:

Previous prospective studies have found an association between prolactin (PRL) levels and increased risk of breast cancer. Using data from a population-based breast cancer case–control study conducted in two cities in Poland (2000–2003), we examined the association of PRL levels with breast cancer risk factors among controls and with tumour characteristics among the cases.

Methods:

We analysed PRL serum levels among 773 controls without breast cancer matched on age and residence to 776 invasive breast cancer cases with available pretreatment serum. Tumours were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis. Breast cancer risk factors, assessed by interview, were related to serum PRL levels among controls using analysis of variance. Mean serum PRL levels by tumour characteristics are reported. These associations also were evaluated using polytomous logistic regression.

Results:

Prolactin levels were associated with nulliparity in premenopausal (P=0.05) but not in postmenopausal women. Associations in postmenopausal women included an inverse association with increasing body mass index (P=0.0008) and direct association with use of recent/current hormone therapy (P=0.0006). In case-only analyses, higher PRL levels were more strongly associated with lobular compared with ductal carcinoma among postmenopausal women (P=0.02). Levels were not different by tumour size, grade, node involvement or oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status.

Conclusions:

Our analysis demonstrates that PRL levels are higher among premenopausal nulliparous as compared with parous women. Among postmenopausal women, levels were higher among hormone users and lower among obese women. These results may have value in understanding the mechanisms underlying several breast cancer risk factor associations.     

Amphiregulin and Epiregulin mRNA expression in primary colorectal cancer and corresponding liver metastases

Background

A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics.

Methods

Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models.

Results

No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users.

Conclusion

Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.